Effect of alpha-methyldopa on dopamine synthesis and release in rat striatum in vitro

The effect of alpha-methyldopa and alpha-methyldopamine (alpha-MDA) on the rate of hydroxylation of radioactive tyrosine was studied in striatal slices from rat brain. This was done by measuring the formation of 3-H-H2O as well as the accumulation of 3-H-dopamine (3-H-DA) from L-3, 5-3-H-tyrosine. alpha-Methyldopa, at tissue concentrations similar to those found in vivo after systemic administration, produced a decrease in both 3-H-H2O and 3-H-DA. The marked decrease (91thyldopa injection, also inhibited 3-H-H2O formation. The inhibitory effect of alpha-methyldopa on 3-H-H2O formation was not reduced by the addition of brocresine, which prevents the formation of alpha-MDA. The effects of alpha-methyldopa and alpha-MDA on the release of 3-H-DA that had been taken up into brain slices, was also studied. Although alpha-methyldopa, 1000 muM, did not increase the release of 3H-DA from tissue, alpha-MDA did. However, the latter was more potent in inhibiting 3-H-H2O formation from 3-H-tyrosine than in releasing 3-H-DA. These results, as well as the close similarity between the percent reduction of 3-H-H2O formation and tissue 3-H-DA levels, suggest that alpha-methyldopa decreases tissue levels of dopamine by inhibiting tyrosine hydroxylase activity in DA neurons.